title: Recent advances in the epidermal growth factor receptor/ligand system biology on skin homeostasis and keratinocyte stem cell regulation.
abstract: The epidermal growth factor (EGF) receptor/ligand system stimulates multiple pathways of signal transduction, and is activated by various extracellular stimuli and inter-receptor crosstalk signaling. Aberrant activation of EGF receptor (EGFR) signaling is found in many tumor cells, and humanized neutralizing antibodies and synthetic small compounds against EGFR are in clinical use today. However, these drugs are known to cause a variety of skin toxicities such as inflammatory rash, skin dryness, and hair abnormalities. These side effects demonstrate the multiple EGFR-dependent homeostatic functions in human skin. The epidermis and hair follicles are self-renewing tissues, and keratinocyte stem cells are crucial for maintaining these homeostasis. A variety of molecules associated with the EGF receptor/ligand system are involved in epidermal homeostasis and hair follicle development, and the modulation of EGFR signaling impacts the behavior of keratinocyte stem cells. Understanding the roles of the EGF receptor/ligand system in skin homeostasis is an emerging issue in dermatology to improve the current therapy for skin disorders, and the EGFR inhibitor-associated skin toxicities. Besides, controlling of keratinocyte stem cells by modulating the EGF receptor/ligand system assures advances in regenerative medicine of the skin. We present an overview of the recent progress in the field of the EGF receptor/ligand system on skin homeostasis and regulation of keratinocyte stem cells.
authors.affiliation: Senior Research Fellow Center, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan; Department of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan. Electronic address: nanba8@m.ehime-u.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nanba
authors.forename: Fujio
authors.initials: F
authors.lastname: Toki
authors.forename: Yann
authors.initials: Y
authors.lastname: Barrandon
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
mesh_terms: D000818:Animals; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000502:physiology*; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D012038:Regeneration; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D012879:Skin Physiological Phenomena; D013234:Stem Cells / Q000166:cytology
chemical_list: D008024:Ligands; D010455:Peptides; D004815:Epidermal Growth Factor; D066246:ErbB Receptors
keywords: EGF; EGFR; Growth factor signaling; Keratinocyte stem cells; Keratinocytes